Discussion

Rhabdomyoma is the most common cardiac tumour in paediatric age group. The reported prevalence of cardiac rhabdomyoma varies from 0.002 to 0.25% in necropsy series, 0.02 to 0.08% in live-born infants, and 0.12% in prenatal fetal studies. ^{Reference Isaacs3} Most cases are asymptomatic and undergo spontaneous regression. Depending upon their location, rhabdomyomas may interfere with myocardial function by causing mechanical obstruction of the outflow tracts, valve regurgitations, and arrhythmias including pre-excitation.

The option of mTOR (mammalian target of rapamycin) inhibitors like everolimus in the management of cardiac rhabdomyomas is an evolving concept and is described as case reports or small case series in literature. ^{Reference Dahdah4– Reference Breathnach, Pears, Franklin, Webb and McMahon11} Nespoli et al. described the use of everolimus in a neonate with multiple biventricular cardiac rhabdomyomas, causing subaortic obstruction. Everolimus therapy was given for 6 months and showed regression of the intracardiac masses and normalisation of trans-aortic gradients. ^{Reference Nespoli, Albani and Corti7} Babaoğlu et al. reported the efficacy of everolimus therapy in seven neonates (median age 8 days) diagnosed with cardiac rhabdomyoma, who were treated with different dose regimens. The indication of everolimus therapy was inflow/outflow obstruction in six patients and supraventricular tachycardia resistant to antiarrhythmic drugs in one patient. Everolimus was administered in a dose of 0.25 mg two times a day for 2 days a week in four patients, 0.1 mg/day in two patients, and 0.4 mg/day in one patient. Significant regression of cardiac rhabdomyoma was observed in all patients, and the tachycardia was controlled in 2 weeks after everolimus initiation. ^{Reference Babaoğlu, Başar, Usta, Yılmaz and Günlemez8} Breathnach et al. described a neonate with severe left ventricular outflow tract obstruction secondary to a large rhabdomyoma infiltrating the paraaortic area, extending around the origin of the right coronary artery making surgical resection difficult. Oral sirolimus therapy (0.5 mg once daily) resulted in a rapid regression of the tumour within 1 month of treatment. ^{Reference Breathnach, Pears, Franklin, Webb and McMahon11} Ng et al. reported outcomes of the use of mTOR inhibitors in a group of six patients with cardiac rhabdomyomas ^{Reference Ng, McGuinness and Prendiville12} . The starting dose for everolimus varied from 0.9 to 2.3 mg/m² per day. In five patients, there was a significant reduction in the size of rhabdomyoma with therapy with everolimus. Cleary et al. summarised the current evidence about the use of everolimus in neonatal cardiac rhabdomyomas in a meta-analysis. There were significant differences in the dosage regimes and monitoring strategies. The most commonly used drug maintenance levels for everolimus was 5–15 ng/ml. The majority received treatment for 1–6 months. Dyslipidaemia was the most commonly reported side effect. ^{Reference Cleary and McMahon13}

Our case had a haemodynamically significant cardiac rhabdomyoma in the left ventricle, which was compromising both the inflow and outflow with a high potential for acute life-threatening events (Figures 1 and 2). Even though the diagnosis was made in the prenatal stage, everolimus was not initiated prenatally since the tumour was haemodynamically well tolerated and considering the fact that this is still experimental in the prenatal stage. Though the dosage regime we used was lower than most of the published reports, we could achieve the recommended drug levels and the desired clinical response. Everolimus therapy resulted in a dramatic reduction in the tumour size within 3 weeks of initiation without causing any adverse effects (Figure 2, Movie 1). Although the previous case reports have documented regression of tumour size with the use of everolimus, such a rapid and dramatic regression in a massive left ventricular rhabdomyoma is a strikingly noteworthy clinical response. Though the patient did not have any neurological symptoms or signs till now, an MRI of the brain is planned on follow-up in view of the strong association reported between cardiac rhabdomyomas and central nervous system involvement. ^{Reference Northrup, Aronow and Bebin14}

In conclusion, everolimus is an effective therapy for promoting tumour regression in haemodynamically significant cardiac rhabdomyomas in neonates and should be considered in large tumours causing blood flow obstructions or significant arrhythmias.